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Am J Pathol. 2019 Feb;189(2):272-282. doi: 10.1016/j.ajpath.2018.10.009. Epub 2018 Nov 16.

Hepatocyte Peroxisome Proliferator-Activated Receptor α Enhances Liver Regeneration after Partial Hepatectomy in Mice.

Author information

1
School of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, Hefei, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Capital Medical University, Beijing, China.
2
Department of Geriatrics, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
3
Department of Infectious Diseases, Peking University First Hospital, Beijing, China.
4
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Capital Medical University, Beijing, China.
5
Laboratory of Metabolism, National Cancer Institute, NIH, Bethesda, Maryland.
6
School of Pharmacy, Anhui Provincial Hospital, Anhui Medical University, Hefei, China; Department of Oncology, First Affiliated Hospital, Anhui Medical University, Hefei, China; Institute for Liver Diseases, Anhui Medical University, Hefei, China. Electronic address: wanghua@ahmu.edu.cn.
7
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Capital Medical University, Beijing, China. Electronic address: aijuanqu@ccmu.edu.cn.

Abstract

Peroxisome proliferator-activated receptor α (PPARα) is a key nuclear receptor involved in the control of lipid homeostasis. In rodents, PPARα is also a potent hepatic mitogen. Hepatocyte-specific disruption of PPARα inhibits agonist-induced hepatocyte proliferation; however, little is known about the exact role of PPARα in partial hepatectomy (PHx)-induced liver regeneration. Herein, using hepatocyte-specific PPARα-deficient (PparaΔHep) mice, the function of hepatocyte PPARα in PHx-induced liver regeneration was investigated. PPARα protein level and transcriptional activity were increased in the liver after PHx. Compared with the Pparafl/fl mice, PparaΔHep mice exhibited significantly reduced hepatocyte proliferation at 32 hours after PHx. Consistently, reduced Ccnd1 and Pcna mRNA and CYCD1 and proliferating cell nuclear antigen protein were observed at 32 hours after PHx in PparaΔHep mice. Furthermore, PparaΔHep mice showed increased hepatic lipid accumulation and enhanced hepatic triglyceride contents because of impaired hepatic fatty acid β-oxidation when compared with that observed in Pparafl/fl mice. These results indicate that PPARα promotes liver regeneration after PHx, at least partially via regulating the cell cycle and lipid metabolism.

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